Last update 01 Nov 2024

NPY4R x NPY2R

Last update 01 Nov 2024

Basic Info

Related Targets

NPY4RNPY2R

Drugs associated with NPY4R x NPY2R

Obinepitide

Target

NPY2R x NPY4R

Mechanism

NPY2R agonists [+1]

Active Org.-

Originator Org.

7TM Pharma

Active Indication-

Inactive Indication

Obesity

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with NPY4R x NPY2R

EUCTR2007-000993-22-SE / Not yet recruitingNot Applicable

A multi-centre, randomized, double-blind, placebo-controlled, parallel-group study in obese subjects investigating weight loss after repeated, subcutaneous doses of TM30338

Start Date02 May 2007

Sponsor / Collaborator

7TM A/S

100 Clinical Results associated with NPY4R x NPY2R

100 Translational Medicine associated with NPY4R x NPY2R

0 Patents (Medical) associated with NPY4R x NPY2R

Literatures (Medical) associated with NPY4R x NPY2R

20 Feb 2023·Yi chuan = Hereditas

Adipocyte reconstitution of Npy4r gene in Npy4r silenced mice promotes diet-induced obesity.

Article

Author: Li, Min-Dian ; Lin, Shu ; Huang, Rong-Feng ; Wang, Lan ; Zhang, Zhi-Hui ; Zeng, Fan

Neural regulation of adipose tissue is crucial in the homeostasis of energy metabolism. Adipose tissue neuropeptide Y (NPY) and its receptors contribute to the development of diet-induced obesity. NPY1R and NPY2R are major receptors for NPY in peripheral tissues including the adipose tissue. NPY receptor 4 (Npy4r) gene is expressed in adipose tissue. However, it is unknown whether Npy4r is involved in the development of diet-induced obesity. Here, we established an immunofluorescence microscopy technique and generated an adipocyte-reconstituted Npy4r gene knockout mouse. Among six adipose depots, we found that NPY is highly expressed around the vasculature in a dot-like fashion in interscapular brown fat and subcutaneous fat, and NPY receptors are expressed in a depot-specific manner. NPY1R is highly expressed in epidydimal fat, interscapular and peri-aortic brown fat, NPY2R in both interscapular and peri-aortic brown fat, and NPY4R in both brown fat and epidydimal fat. Next, we showed that adipocyte-reconstituted expression of Npy4r promoted diet-induced obesity in mice (P < 0.0001). Overall, this study defines the abundance and distribution of NPY and its receptors 1, 2, and 4 in mouse adipose depots, and demonstrates in an adipocyte-reconstituted gene knockout model that adipocyte Npy4r is sufficient to promote diet-induced obesity.

01 Jan 2022·Progress in Neuro-Psychopharmacology and Biological PsychiatryQ2 · MEDICINE

Effect of depression and suicidal behavior on neuropeptide Y (NPY) and its receptors in the adult human brain: A postmortem study

Q2 · MEDICINE

Article

Author: Pandey, Ghanshyam N ; Ren, Xinguo ; Sharma, Anuradha ; Zhang, Hui

Neuropeptides are small proteinaceous molecules (3-100 amino acids) that are secreted by neurons and act on both neuronal and non-neuronal cells. Neuropeptide Y (NPY), a highly conserved and expressed neuropeptide in the central nervous system of mammals, plays a major role in stress response and resilience. Increasing evidence suggests that NPY and its receptors are altered in depression and suicide, pointing to their antidepressant-like nature. The objective of this study was to examine the role of NPY system in depression and suicidal behavior. Expression of NPY and its four receptors, NPY1R, NPY2R, NPY4R, and NPY5R was studied at the transcriptional and translational levels in the prefrontal cortex (PFC) and hippocampus regions of the postmortem brain of normal control (NC) (n = 24) and depressed suicide (DS) (n = 24) subjects. We observed a significant decrease in NPY mRNA and upregulation in NPY1R and NPY2R mRNA in both brain regions of DS subjects compared with NC subjects. We also observed a significant decrease in NPY protein expression in the PFC of subjects with DS. This study provides the first detailed evidence of alterations in the NPY system and the associated stress response in depression and suicidal behavior in humans. The outcomes of this study could be applied in the development of novel NPY system-targeted approaches for the treatment of depression.

01 Nov 2019·EndocrinologyQ2 · MEDICINE

Modified Peptide YY Molecule Attenuates the Activity of NPY/AgRP Neurons and Reduces Food Intake in Male Mice

Q2 · MEDICINE

Article

Author: Jones, Edward S ; Østergaard, Søren ; Chambers, Adam P ; Luckman, Simon M ; Nunn, Nicolas ; Wulff, Birgitte S

AbstractTo study the effects of an analog of the gut-produced hormone peptide YY (PYY3-36), which has increased selectivity for the Y2 receptor; specifically, to record its effects on food intake and on hypothalamic neuropeptide Y/agouti-related peptide (NPY/AgRP) neuron activity. NNC0165-1273, a modified form of the peptide hormone PYY3-36 with potent selectivity at Y2 receptor (>5000-fold over Y1, 1250-fold over Y4, and 650-fold over Y5 receptor), was tested in vivo and in vitro in mouse models. NNC0165-1273 has fivefold lower relative affinity for Y2 compared with PYY3-36, but >250-, 192-, and 400-fold higher selectivity, respectively, for the Y1, Y4, and Y5 receptors. NNC0165-1273 produced a reduction in nighttime feeding at a dose at which PYY3-36 loses efficacy. The normal behavioral satiety sequence observed suggests that NNC0165-1273 is not nauseating and, instead, reduces food intake by producing early satiety. Additionally, NNC0165-1273 blocked ghrelin-induced cFos expression in NPY/AgRP neurons. In vitro electrophysiological recordings showed that, opposite to ghrelin, NNC0165-1273 hyperpolarized NPY/AgRP neurons and reduced action potential frequency. Administration of NNC0165-1273 via subcutaneous osmotic minipump caused a dose-dependent decrease in body weight and fat mass in an obese mouse model. Finally, NNC0165-1273 attenuated the feeding response when NPY/AgRP neurons were activated using ghrelin or more selectively with designer receptors. NNC0165-1273 is nonnauseating and stimulates a satiety response through, at least in part, a direct action on hypothalamic NPY/AgRP neurons. Modification of PYY3-36 to produce compounds with increased affinity to Y2 receptors may be useful as antiobesity therapies in humans.

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